This Mentored Research Scientist Development Award will support the candidate in transitioning into an independent investigator in translational research with a focus on mood disorders. With a background in animal research, the candidate proposes training in human functional magnetic resonance imaging (fMRI) to investigate brain activity associated with social rejection and acceptance. Social rejection (an explicit declaration that an individual is not liked) has powerful effects on emotion and behavior including lowered self- esteem, major depression, risk-taking behavior, substance abuse, and violence. A few fMRI studies have found increased activity in the anterior cingulate cortex using different paradigms for social rejection. The first aim of the project is to test experimental manipulations for social rejection, explore its parameters, and adapt a stimulus presentation for use in fMRI experiments. The second aim is to use fMRI to examine neuronal pathways involved in social rejection. Based on anatomical pathways found in rats and monkeys, it is hypothesized that in addition to the anterior cingulate cortex, activation will be found in the periaqueductal gray, thalamus, amygdala, nucleus accumbens, and subgenual cortex. These structures are known to be involved in stress responses and major depression, as well as responding to rewards. An exploratory aim will assess behavioral responses to social rejection in patients with Major Depressive Disorder (MDD) without fMRI. Once the behavioral responses are studied, my long-term goal is to examine abnormal neuronal responses to social rejection in MDD with neuroimaging. Atypical depression, for example, is uniquely characterized by intense social rejection sensitivity. Identifying a unique biological profile for a depressive subtype may improve its definition, diagnosis, and treatment. PUBLIC HEALTH RELEVANCE: Social rejection can lead to major depression and social anxiety. This proposal seeks to understand how the brain processes social rejection. The results may help us to identify those who are vulnerable to the effects of social rejection, and lead to innovative treatments and preventive measures.